Alpha-NETA, as a CMKLR1 Small Molecule Antagonist, Protects against
Renal Ischemia Reperfusion Injury in Mice

Xue      Peng; Wenjuan      Wang; Wenhao      Wang; Jingrui      Qi

doi:10.2174/0929866529666220822095950

Abstract

Background: Ischemia-reperfusion (IR) injury is one of the major causes of acute kidney injury (AKI). Chemerin chemokine-like receptor 1 (CMKLR1) has been reported to be involved in the progression of IR injury. Here, we investigated the protective role of CMKLR1 antagonist, α-NETA, in IR mouse model, and dissected the underlying regulatory mechanism.

Methods: IR injury mouse model was established to evaluate the protective effects of α-NETA on IR injury. Kidney injury-associated parameters and functions were examined to evaluate the renal function of Sham, IR, and IR+ α-NETA mice. Renal morphological changes and apoptosis were determined by PAS and TUNEL staining in IR and α-NETA treated mice. ELISA, RT-qPCR, and western blot were performed to examine the inflammatory responses and expression of CMKLR1.

Results: α-NETA administration attenuated IR-induced renal tubular injury and epithelial cell apoptosis in IR injury mice. Kidney injury-related cystatin C, kidney injury molecule-1, neutrophil gelatinaseassociated lipocalin, and renal morphology were significantly improved. Mechanistically, α-NETA suppressed the inflammatory responses by inhibiting the expression of CMKLR1, and then protected the IR-induced renal damage and restored renal function.

Conclusion: CMKLR1 plays an important role in renal ischemia-reperfusion injury, targeting CMKLR1 by using the small molecule inhibitor α-NETA is a potential treatment strategy for AKI.

Keywords: ischemia reperfusion injury, CMKLR1, α-NETA, apoptosis inflammation

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DOI https://dx.doi.org/10.2174/0929866529666220822095950	Print ISSN 0929-8665
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Alpha-NETA, as a CMKLR1 Small Molecule Antagonist, Protects against Renal Ischemia Reperfusion Injury in Mice

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